Significance Current treatments for autoimmune diseases rely on nonspecific immunosuppression, risking important complications and limiting the long-term use of these approaches for the treatment of chronic human autoimmunity. Thus, there is an unmet need for therapeutic approaches to reestablish immune tolerance in autoimmune disorders in an antigen-specific manner. Here, we describe a nanoliposome (NLP)-based platform for the induction of antigen-specific tolerance via the modulation of signaling by the aryl hydrocarbon receptor. These NLPs suppress disease pathology and pathogenic autoimmunity in preclinical models of multiple sclerosis, providing a candidate antigen-specific therapeutic approach for the management of autoimmune disorders.